Our Approach & Expertise

	Members of the Leukemia Team

Over the past four decades, our Center has pioneered many new chemotherapy regimens that have increased the long-term disease-free survival rates of children and young adults. Because of these excellent results, our therapy regimens have been adopted worldwide.

It is important for treatments to be designed specifically for younger people. Young adults, when given age-appropriate treatment protocols, have a much better long-term outcome than when they are treated on regimens designed for older patients.

Our Center was the first to recognize that the initial response to therapy could be used as a tool for selecting the most appropriate therapy for a child with leukemia. Patients who experience a rapid early response -- which indicates a probable favorable outcome -- are treated with less-intensive therapy, and that means fewer side effects. Our physicians recognized early on that in addition to acute short-term side effects, some treatments have the potential to cause problems years later, long after therapy is over. Our Center works to successfully treat patients with the lowest effective dose of chemotherapy to avoid long-term problems with side effects.

Treatment Innovations that Minimize Long-Term Side-Effects

• Our physicians were among the first to seek to avoid the use of brain irradiation for central nervous system prophylaxis in most children in an effort to prevent possible learning disabilities and other side effects. Our physicians started a unique protocol for the treatment of central nervous system leukemia that does not use any cranial irradiation.

• Studies that originated here demonstrated that the anthracycline drugs have late cardiac toxicity, but studies also established that there are ways to administer anthracylines to minimize this problem.

• With the help of the vast laboratory facilities at our Center, the Pediatric Hematolgic Malignancy Team works to develop new therapeutic approaches. Each patient's leukemic cells are analyzed extensively for their surface and chromosome markers and for their ability to grow and respond to treatment in animals. Cells are tested for the way they metabolize chemotherapy drugs. Knowing as much as possible about a patient's leukemia cells can help doctors decide on the best course of treatment for each patient. We test the genetic makeup of leukemia cells, looking for certain markers that tell us whether the cells are multi-drug resistant and whether the cells undergo programmed cell death the way healthy cells do.

• We are also working on new ways to use the patient's own immune system to fight the leukemia. We grow the patient's own immune cells (T cells) in culture and try to develop the T cells' ability to recognize and kill the leukemia cells. We hope to use these cells in the future in combination with chemotherapy to eliminate disease that may be left behind once chemotherapy is completed.

For more than 25 years, our pediatrics team has advocated approaches to treatment that reduce the anxiety and many other psychological side effects of cancer therapy. All painful procedures are performed while the patient is under brief anesthesia. Most therapy is administered on an outpatient basis.

Relapse

We are currently evaluating a new combination of drugs for patients in relapse. These medicines have been used extensively to treat other cancers but are not usually used to treat leukemia. Patients who have relapsed many times, or who have refractory disease, have leukemic cells that have become resistant to previously used treatments, but the cells may still respond to new drugs. The combination of topotecan, vinorelbine, thiotepa, and gemcitabine shows a 45 percent response rate in heavily pretreated patients with refractory disease.

Latest Research Directions

For patients who have exhausted all known effective therapies, our Hematologic Malignancy Team may have new drug trials available. Dr. Steinherz has designed and chaired many international cooperative group clinical trials for the treatment of leukemia.

Our investigators are conducting a study aimed at improving the current standard treatment for AML and ALL to see if more children can be cured. The standard treatment includes a drug called methotrexate given by mouth, followed by one period of intensive therapy with many drugs (this period is called "delayed intensification"). Some patients in the study will receive two delayed intensification periods; others may receive a higher dose of methotrexate by vein. The study will compare the effectiveness and side effects of the different treatments. More drugs may be more effective, but they may also have more side effects. While doctors would like to determine the optimal combination of chemotherapy drugs they are also seeking to find what will cure the most patients with minimum side effects.